Synthesis, characterization, DNA binding, cleavage activity and cytotoxicity of copper(ii) complexes (original) (raw)
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DNA Binding, DNA Cleavage, and Cytotoxicity Studies of Two New Copper (II) Complexes
DNA and Cell Biology, 2011
The DNA binding behavior of [Cu(phen)(phen-dione)Cl]Cl (1) and [Cu(bpy)(phen-dione)Cl]Cl (2) was studied with a series of techniques including UV-vis absorption, circular dichroism spectroscopy, and viscometric methods. Cytotoxicity effect and DNA unwinding properties were also investigated. The results indicate that the Cu(II) complexes interact with calf-thymus DNA by both partially intercalative and hydrogen binding. These findings have been further substantiated by the determination of intrinsic binding constants spectrophotometrically, 12.5Â10 5 and 5Â10 5 for 1 and 2, respectively. Our findings suggest that the type of ligands and structure of complexes have marked effect on the binding affinity of complexes involving CT-DNA. Circular dichroism results show that complex 1 causes considerable increase in base stacking of DNA, whereas 2 decreases the base stacking, which is related to more extended aromatic area of 1,10-phenanthroline in 1 rather than bipyridine in 2. Slow decrease in DNA viscosity indicates partially intercalative binding in addition to hydrogen binding on the surface of DNA. The second binding mode was also confirmed by additional tests: interaction in denaturation condition and acidic pH. Also, these new complexes induced cleavage in pUC18 plasmid DNA as indicated in gel electrophoresis and showed excellent antitumor activity against K562 (human chronic myeloid leukemia) cells.
Spectrochimica Acta Part A-molecular and Biomolecular Spectroscopy
The DNA binding behavior of [Cu(phen)(phen-dione)Cl]Cl (1) and [Cu(bpy)(phen-dione)Cl]Cl (2) was studied with a series of techniques including UV-vis absorption, circular dichroism spectroscopy, and viscometric methods. Cytotoxicity effect and DNA unwinding properties were also investigated. The results indicate that the Cu(II) complexes interact with calf-thymus DNA by both partially intercalative and hydrogen binding. These have been further substantiated by the determination of intrinsic binding constants spectrophotometrically, 12.5Â10 5 and 5Â10 5 for 1 and 2, respectively. Our findings suggest that the type of ligands and structure of complexes have marked effect on the binding affinity of complexes involving CT-DNA. Circular dichroism results show that complex 1 causes considerable increase in base stacking of DNA, whereas 2 decreases the base stacking, which is related to more extended aromatic area of 1,10-phenanthroline in 1 rather than bipyridine in 2. Slow decrease in DNA viscosity indicates partially intercalative binding besides hydrogen binding on DNA surface. The second binding mode was also confirmed by additional tests: interaction in denaturation condition and acidic pH. Also, these new complexes induced cleavage in pUC18 plasmid DNA as indicated in gel electrophoresis and showed excellent antitumor activity against K562 (human chronic myeloid leukemia) cells.
Polyhedron, 2007
Mixed ligand complexes having the formulae Cu(RPO) 2 Py 2 , Cu(RPO) 2 Im 2 and Cu(DBO) 2 Py 2 [RPO = resacetophenone oxime, DBO = 2,4-dihydroxybenzophenone oxime, Py = pyridine and Im = imidazole] have been synthesized and characterized by UV-Vis, IR, ESR, cyclic voltammetry and magnetic susceptibility methods. Absorption studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of 10 4 -10 5 M À1 . Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of the adducts was carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H 2 O 2 ). All the metal complexes cleaved supercoiled DNA by hydrolytic and oxidative paths. The oxidative path dominates the hydrolytic cleavage. The hydrolytic cleavage of DNA is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO or the singlet oxygen quencher azide ion.
Medicinal Chemistry Research, 2014
Two ternary copper(II) complexes of DL-threonine and polypyridyl ligands with formula of [Cu(Thr) (Byp)Cl]ÁH 2 O (1) and [Cu(Thr)(Phen)H 2 O]ClÁ2H 2 O were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV-Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d-d electronic band in the range of 610-620 nm in Tris-HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (K b ) of (1) and (2) were 0.5 and 4.4 9 10 5 M -1 , respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H 2 O 2 . The results showed that (2) has the highest DNA binding and nuclease activity.
Inorganic Chemistry, 2011
Two mononuclear fluorophore-labeled copper(II) complexes [Cu(nip)(acac)] þ (2) and [Cu(nip) 2 ] 2þ (3), where fluorophore is 2-(naphthalen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (nip) (1) and acac is acetylacetone, have been synthesized and characterized by various techniques. The ligand 1 and complex 2 are structurally characterized by single-crystal X-ray diffraction. The coordination geometries around the copper are square planar in solid as well as solution state as evidenced by electron paramagnetic resonance (EPR) spectroscopy. The density functional calculations carried out on 1-3 have shown that electron-rich regions in the highest occupied orbital are localized on the naphthalene and partly on the phenanthroline moiety. Both complexes 2 and 3 in dimethyl sulfoxide (DMSO) exhibit near square planar structure around the metal ion in their ground state. Time-dependent density functional theory (TD-DFT) calculations reveal that Cu(II) ion in complex 2 shows tetrahedral coordination around the metal while 3 retains its square planar geometry in the lowest excited state. The interaction of complexes with calf-thymus DNA (CT DNA) has been explored by using absorption, emission, thermal denaturation, and viscosity studies, and the intercalating mode of DNA binding has been proposed. The complexes cleave DNA oxidatively without any exogenous additives. The protein binding ability has been monitored by quenching of tryptophan emission in the presence of complexes using bovine serum albumin (BSA) as model protein. The compounds showed dynamic quenching behavior. Further, the anticancer activity of the complexes on MCF-7 (human breast cancer), HeLa (human cervical cancer), HL-60 (human promyelocytic leukemia), and MCF-12A (normal epithelial) cell lines has been studied. It has been observed that 3 exhibits higher cytotoxicity than 2, and the cells undergo apoptotic cell death.
Polyhedron, 2011
The copper complexes [Cu(Pyimpy)(H 2 O)](ClO 4 ) 2 (1), [Cu(Pyimpy) 2 ](ClO 4 ) 2 (2), [Cu(Pyimpy)(Cl) 2 ]Á2H 2 O (3Á2H 2 O), [Cu(Pyimpy)(N 3 )(ClO 4 )] 2 (4) and [Cu(Pyimpy)(SCN)(ClO 4 )] 2 (5) were synthesized and characterized by spectroscopic techniques, crystal structures and electrochemical studies (Pyimpy: (2-((2-phenyl-2-(pyridin-2-l)hydrazono)methyl)pyridine)). The superoxide scavenging activity of the two water soluble complexes 1 and 3 was examined. DNA interaction studies by UV-Vis absorption spectral changes during a titration experiment indicated the generation of new species. These small molecule SOD mimics exhibited excellent DNA cleavage activity in the presence of H 2 O 2 as well as 2-mercaptoethanol. Complexes 1-5 exhibited better cytotoxicity compared to CuCl 2 Á2H 2 O and the ligand Pyimpy, and showed more potency than cisplatin for MCF-7, PC-3 and HEK-293 cells. Complex 3 exhibited the highest potency for MCF-7, PC-3 and HEK-293 cells compared to the other complexes.
Copper(II) complexes with simple and mixed ligands, [Cu(L)(ClO 4)] (1) and [Cu(L)(diimine)]ClO 4 (2–4) [where L is 4-chloro-2-((2-(phenylthio)phenylimino)methyl)phenol and diimine is 1,10-phenanthroline (phen, 2), 2,2 0-bipyridine (bpy, 3) or 4,4 0-dimethyl-2,2 0-bipyridyl (dmbpy, 4)], were synthesized and characterized by elemental analysis, UV-vis, FT-IR, electrospray ionization-mass spectrometry (ESI-MS) and electrochemical studies. Notably, complex 4 was structurally characterized using single X-ray crystallography. It was observed that this complex has a slightly distorted square planar geometry. The varying interactions of these complexes with herring sperm DNA (HS-DNA) were explored in detail using various spectral and electrochemical methods to gain insight into their structure–activity relationships. The obtained results revealed that complexes 1, 3 and 4 could interact with HS-DNA via a partial intercalation mode, whereas complex 2 was found to deeply stack between base pairs with a binding constant of 10 4 M À1 due to its enhanced planarity; moreover, 4 underwent a hydrophobic interaction with DNA. These experimental observations were found to be close to the theoretical observations investigated by the molecular docking technique. The interaction of these synthesized Cu(II) complexes with bovine serum albumin (BSA) was also evaluated using absorption and fluorescence techniques, which revealed a static quenching mechanism between the complexes and BSA. In addition, DNA cleavage by the complexes was monitored by electrophoretic spectrometry; the results showed that these complexes exhibited significant cleavage in the presence of a reducing agent (ascorbic acid). The in vitro cytotoxicity of these Cu(II) complexes was carried out in two different human tumour cell lines, A549 and Huh7. Furthermore, molecular docking was also used to evaluate and understand the interaction modes of the complexes with the molecular target DNA. All the in vitro pharmacological evaluation observations clearly indicated the superior DNA binding/cleaving and protein binding properties of these complexes, although the S-donor atom did not coordinate with the central copper ion in the mixed complexes.
2-(1H-Tetrazol-5-yl)pyridine (L) has been reacted separately with Me2NCH2CH2Cl·HCl and ClCH2CH2OH to yield two regioisomers in each case, N,N-dimethyl-2-[5-(pyridin-2-yl)-1H-tetrazol-1- yl]ethanamine (L1)/N,N-dimethyl-2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanamine (L2) and 2-[5-(pyridin- 2-yl)-1H-tetrazol-1-yl]ethanol (L3)/2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanol (L4), respectively. These ligands, L1–L4, have been coordinated with CuCl2·H2O in 1: 1 composition to furnish the corresponding complexes 1–4. EPR Spectra of Cu complexes 1 and 3 were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single X-ray crystallographic studies of 3 revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymusDNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on doublestranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative free-radical mechanism (OH·). In vitro anticancer activities of the complexes against MCF-7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. The IC50 values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin.
Journal of Coordination Chemistry, 2013
A series of Cu(II) complexes of 5,5-dimethyl-2-(2-arylhydrazono)cyclohexane-1,3-dione (HL n) were synthesized by the coupling of dimedone with aniline and its derivatives. These ligands and their Cu(II) complexes were characterized by elemental analyses, IR, 1 H NMR, 13 C NMR, UV-Visible, X-ray diffraction analysis and magnetic measurements. Spectral studies revealed that the ligand exist in an internally hydrogen bonded keto-hydrazone form rather than the azo-enol form. The ligands (HL n) acts as a monobasic bidentate ligand by coordinating via the nitrogen atom of the hydrazone moiety (-NH-) with deprotonation and oxygen atom of the carbonyl (C=O) group. The optimized bond lengths, bond angles and quantum chemical parameters of the complexes were calculated. The calf thymus DNA binding activity of the ligands and their Cu(II) complexes were studied by absorption spectra and viscosity measurements. The antimicrobial activities of ligands and Cu(II) complexes were tested against gram negative bacteria (Escherichia coli), gram positive bacteria (Staphylococcus aureus) and fungal (Candida albicans). The cytotoxic activity of ligands and Cu(II) complexes was tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). The antioxidant activities of ligands and Cu(II) complexes were performed by ABTS method.